Olanzapine is an atypical antipsychotic medication and a very effective treatment for schizophrenia. However, it is associated with third highest incidence of neutropenia among all antipsychotics, and this may limit its use. We present a case of a schizophrenic female who was successfully treated with olanzapine and lithium to enhance white blood cells after a history of neutropenia caused by olanzapine treatment. We briefly discuss the use of lithium in patients who were rechallenged with antipsychotic medications. This case study supports the use of lithium for olanzapine-induced neutropenia as a successful and safe strategy.

Olanzapine is an atypical antipsychotic medication used to treat schizophrenia and other related psychiatric disorders. Although olanzapine could be the most effective treatment after clozapine in the treatment of schizophrenia,[4] it is associated with the third highest incidence of neutropenia.[5] Therefore, it is a challenge for psychiatrists to switch patients who respond very well to olanzapine to another antipsychotic. Lithium is known to enhance white blood cells (WBCs) and neutrophil counts. Furthermore, it is reported that lithium speeds the recovery of WBC after development of clozapine-induced agranulocytosis. Due to that, it has been used successfully in chemotherapy patients and clozapine patients who develop neutropenia to continue their treatments.[6] Here, we present an interesting and exceptional schizophrenic female case who was successfully treated with olanzapine and lithium to enhance WBCs after a history of neutropenia was caused by olanzapine treatment.

Case Report

A medically healthy 28-year-old female was presented to Alamal Complex for Mental Health with a history of several years of being isolated, talking to herself, neglecting her self-care, laughing inappropriately, and performing low level of function at home. Two years ago, she had been prescribed oral and injected risperidone (CONSTA ®) at another institution (dose, duration, and adherence unknown), but neither regimen improved her symptoms. Recently, she developed a delusion, believing someone was controlling her emotions, thoughts, and body, forcing her to hate her children and husband. As a result, she developed homicidal intentions against her children and physical aggression toward her husband. She was diagnosed as a case of paranoid schizophrenia. Ten milligrams of olanzapine was prescribed daily. At admission, her WBC and neutrophil counts were 4.86 × 109/L and 1.74 × 109/L, respectively. One month later, these values had decreased to 3.86 × 109/L and 0.93 × 109/L, respectively. After consultation with a hematologist, a full investigation including clinical history, physical examination, and laboratory tests was performed. It was determined that the neutropenia was drug induced. Olanzapine was discontinued immediately. After 1 week of stopping medication, WBC and neutrophil counts increased to 3.84 × 109/L and 1.19 × 109/L, respectively, and lithium (600 mg p.o. daily gradually) was prescribed to enhance neutrophil counts. One week later, her WBC count was 5.32 × 109/L and neutrophil count increased to 1.47 × 109/L. Due to failure of antipsychiatric trials (e.g., risperidone) and good olanzapine response, olanzapine was rechallenged, but this time, the titration was slowly taken from 2.5 mg every 3 days until reaching 10 mg daily. Her symptoms had been improving from week to week. A series of complete blood count (CBC) tests were taken on a weekly basis, and the range of WBCs and neutrophils was 4.72–5.61 × 109/L and 1.32–1.79 × 109/L, respectively. After the patient maintained the improvement and reached the remission stage, we discharged her on a previous regimen, and WBC and neutrophil counts were normal. We gave her an appointment (6 weeks after) in which the last WBC and neutrophil counts were 4.65 × 109/L and 2 × 109/L, respectively.

Discussion

The patient described here had normal WBC and low normal neutrophil counts before starting olanzapine. There was an obvious drop in neutrophil counts after 1 month of starting olanzapine, and this was immediately ameliorated after discontinuing drug use. She had no history of hematological disease or any potential cause of neutropenia (e.g., immunosuppressive medication), and there was a clear temporal relationship between olanzapine use and decreased neutrophil counts that suggests a causal relationship between olanzapine and neutropenia. Management and recovery was limited to discontinue the offending medication as recommended. Since our patient responded significantly to olanzapine but not to other atypical antipsychotics, we considered rechallenging the patient with olanzapine using lithium, while carefully monitoring WBC and neutrophil counts on a weekly basis.

The mechanism of action of olanzapine is still poorly understood, but it may be similar to that of its analog clozapine. Due to this fact, possible mechanisms for inducing leukopenia are toxic or immune mechanisms, genetic predisposition, and inhibition to granulocyte-colony stimulating factors (G-CSF).[7]

The first time of successful use of lithium carbonate to induce WBC counts was in leukopenia due to oncological reasons. It encouraged psychiatrists to use lithium to augment WBC counts during rechallenging patients with clozapine.[8] Mechanism of lithium is unknown but possibly stimulating G-CSF and demargination. Leukocytosis does not seem to be clearly dose related, and it is difficult to measure the extent of its effects.[6]

The concern of clozapine rechallenge is a repeat of blood dyscrasia that could be more fatal than the first dyscrasia. Moreover, combining lithium with clozapine could lead to the development of neurological symptoms (e.g., tremor, involuntary movement) and mask clozapine-induced leukopenia, as documented in some case reports. However, these neurological side effects were transient and occurred in the beginning of the treatment in most cases. Furthermore, it was hard to attribute the cause of blood dyscrasia to clozapine in the mentioned case reports, since those patients were on many medications, such as haloperidol, that could result in leukopenia.[9]

Knan and Kerwin studied 25 patients who were rechallenged with clozapine using lithium following leukopenia or neutropenia during previous therapies. Twenty-four out of 25 patients continued successfully using clozapine with lithium without blood dyscrasia. Only one patient developed blood dyscrasia, but it was shorter and less severe than the first one. They have suggested the following clinical recommendations in case of using lithium for clozapine rechallenge. Lithium should be titrated up until reaching lithium serum level of 0.4 mmol/l. If the result of CBC is normal, clozapine may be started with weekly blood monitoring for the first 18 weeks. If there are any possible signs of infections, the patient has to be examined and repeated CBC is required.[10]

There is no consensus for how long lithium should be used in the augmentation of WBC. Interestingly, lithium has been used successfully for a short period (1 month) in patients who develop leukopenia after the use of paliperidone.[11]

Conclusion

Olanzapine is more likely to cause granulocytopenia than the atypical antipsychotics with exception of clozapine. Therefore, it is recommended that patients who are taking this medication should be carefully monitored. Lithium can be used to enhance WBC in certain conditions, such as in case reported in this study, but the CBC of a patient has to be monitored closely with frequent assessment of signs and symptoms of infection. The role of lithium as an agent in increasing WBCs has to be studied more, and it could be very helpful in treating patients with drug-induced leukopenia.